Published ahead of print on November 4, 2005, doi:10.1164/rccm.200503-344OC
Am. J. Respir. Crit. Care Med., Volume 173, Number 4, February 2006, 421-425
A more recent version of this article appeared on February 15, 2006
Submitted on March 4, 2005
Accepted on November 1, 2005
Impact of Burkholderia Dolosa on Lung Function and Survival in Cystic Fibrosis
Leslie A Kalish1, David A Waltz2, Mark Dovey2, Gail Potter-Bynoe3, Alexander J McAdam4, John J LiPuma5, Craig Gerard2, and Donald Goldmann6*
1 Clinical Research Program, Children's Hospital Boston, Boston, MA, USA,
2 Division of Respiratory Diseases, Children's Hospital Boston, Boston, MA, USA,
3 Infection Control Program, Children's Hospital Boston, Boston, MA, USA,
4 Department of Laboratory Medicine, Children's Hospital Boston, Boston, MA, USA,
5 Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA,
6 Infection Control Program, Children's Hospital Boston, Boston, MA, USA; Infectious Disease Division, Children's Hospital Boston, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: don.goldmann{at}childrens.harvard.edu.
Rationale: Chronic infection with Burkholderia cepacia complex bacteria in cystic fibrosis is associated with accelerated decline in pulmonary function and increased mortality. Clinical implications of the recently characterized genomovar VI, Burkholderia dolosa, are unknown.
Objectives: Characterization of impact of Burkholderia dolosa on pulmonary function and mortality in cystic fibrosis.
Methods: We compared patients chronically infected with Burkholderia dolosa (n=31) to unmatched patients with Burkholderia multivorans (n=24) and to age- and sex-matched controls without Burkholderia species (n=58). We analyzed rates of pulmonary function decline (percent-predicted FEV1) using a random effects model assuming segmented linear trends. All available FEV1 measurements from 5 years (median 4.8) prior until 2.5 years (median 1.5) after the first positive culture for Burkholderia (reference date) were analyzed. Survival was compared using the Kaplan-Meier method and proportional hazards model.
Measurements and Main Results: Baseline FEV1 and rate of decline were similar in the cohorts. Decline in FEV1 following the reference date accelerated in patients with B. dolosa (-2.3 percentage points per year pre vs. -7.1 post, p=0.002), but was unchanged in the B. multivorans and control patients (-2.3 vs. -0.8 post, p=0.38 and -2.1 pre vs. -0.5 post, p=0.20, respectively). The probability of dying within 18 months of the reference date was 13%, 7%, and 3% for B. dolosa, B. multivorans, and control patients, respectively (B. dolosa vs. control hazard ratio 10.8, 95% confidence interval 1.3 to 92.8, p=0.03).
Conclusions: B. dolosa chronic infection in cystic fibrosis is associated with accelerated loss of lung function and decreased survival.
Key words: Burkholderia cepacia complex, Burkholderia multivorans, infection control
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